chapter 1 Flashcards
Is the science that studies DISEASES
pathology
dissection and microscopic examination of human
tissues post-mortem or biopsies from living patients
Anatomic Pathology (aka Morbid Anatomy)
– huge field
– Medical chemistry, microbiology, immunopathology, hematopathology, etc
Clinical Pathology (aka Laboratory Medicine)
deals with “how a disease develops”
Pathogenesis
study of “cause” of a disease
Etiology
Clinical Manifestations
“symptoms”
Membrane-bound digestive organelles ■ Primary lysosome ■ Secondary lysosomes – heterophagosomes – autophagosomes
Lysosomes
Cleans up waste!
– Contain digestive enzymes
Brown pigment composed of oxidized lipids – “Undigested contents of autophagosomes and heterophagosomes” – Accumulates in aging tissues
Give rise to residual bodies (“lipofuscin”)
Definition: adverse conditions that cause a cellular response that remains within the
range of homeostasis
– Injury stops cell returns to it’s original steady state
Caused by brief hypoxia (deficiency of oxygen), brief anoxia (total lack of oxygen) or
low concentration of toxins
Reversible cell injury
Cell’s response to exposure to low doses of
toxins, brief hypoxia or anoxia
– Cellular swelling (hydropic changes – swelling of
cytoplasm and cytoplasmic organelles)
■ A. Normal microvilli
■ B. Swollen microvilli
■ C. Invagination of the cell membrane leading to
formation of membrane-bound vacuoles
■ D. Swollen mitochondria and dilated RER
■ E. Loss of intercellular contact
– Changes in cell membrane permeability
■ Na+/K+ ATPase pump
– Cell returns to original steady state with cessation of injury
Due to cells exposed to heavy doses of toxins,
anoxia or severe or prolonged hypoxia
– Will eventually lead to cell death
Irreversible cell injury
1.Caused by heavy doses of toxins, anoxia and prolonged hypoxia
2.Causes loss of cell integrity and rupture of the cell membrane
3.Dead cells release their contents (especially cytoplasmic enzymes)
into extracellular fluid (blood)
– measured through laboratory blood tests – something is really wrong!
Causes cellular swelling-swelling of cytoplasm and organelles
- Hydropic changes (accumulation of water within the cell)
–2. Anoxia or any energy deprivation causes a decreased function in Na+/K+
pump - Can’t maintain concentration gradient Na+ flows into cell (Cl- follows)
increased [NaCl] INSIDE cell - Water flows easily into cell Swelling
Functional changes that occur in reversible cell injury
- Reduced energy production – swollen mitochondria generate less ATP
- Decreased protein synthesis – pH of cell becomes acidic (due to anaerobic
glycolysis producing lactic acid) which slows metabolism and degranulation of
the RER - Increased autophagy – damaged proteins are phagocytised and lysosomal
enzymes are released. A large amount of this occurring could damage other
cellular components
Causes of Cell Injury
Hypoxia/anoxia
■ Toxins
■ Microbes
■ Inflammation and immune reactions
■ Genetic/metabolic disorders
■ Hypoxia and Anoxia – most common and major cause of cell injury!
– Oxygen is required for cellular respiration
– Low oxygen lowered energy production
– Causes include: Obstruction of airways (suffocation), inadequate oxygen transportation in lung (pneumonia) and
blood (severe anemia), inability of cell to use oxygen for cellular respiration (cyanide poisoning)
■ Re-oxygenation / Re- or postperfusion Injury
– Short lived reversible cell injury due to hypoxia may be repaired by re-oxygenation
– Risk – oxygen toxicity
■ Oxygen radicals formed ionized iron or production of hydrogen peroxide or superoxide
■ Too much oxygen too fast may form oxygen radicals
■ Eg. Post-perfusion myocardial injury or carbon monoxide poisoning
Mediators of Inflammation and Immune Reactions
– Cytokines, interferons, complement proteins
– Eliminate infectious diseases but also kill own body’s cells
– Eg. Autoimmune Diseases such as Systemic Lupus Erythematosus, Grave’s
disease and Myasthenia gravis
■ Genetic and Metabolic Disturbances
– Many genetic diseases cause disturbances to metabolism and accumulation of
toxic metabolites
– Eg. Tay-Sachs Disease (genetic deficiency of Hexosaminidase A – leading to
accumulation of gangliosides in the neurons and eyes); Diabetes Mellitus –
metabolic disturbances of adulthood may lead to various forms of cell injury
Prolonged exposure of cells to negative or exaggerated normal conditions causes various adaptations to: – Cell, tissues, organs ■ Atrophy ■ Hypertrophy ■ Hyperplasia ■ Metaplasia ■ Intracellular accumulations ■ Aging
cell adaptions
Decrease in size of a cell, tissue, organ or entire body
– Can be a reduced size of a cell, reduced number of cells or both
– Aging and damaged organelles are eaten by autophagosomes and digested
■ Undigested residues form lipid-rich brown pigment called lipofuscin
■ Undigested proteins are taken up by ubiquitin (scavenger protein) and marked for
destruction
Atrophy
occurs with age and includes entire body
– Eg. atrophy of thymus after puberty, aging
Physiologic atrophy
occurs as a result of inadequate nutrition or stimulation
– Chronic ischemia, denervation (nerve damage), malnutrition, inactivity
Pathologic atrophy
increase size of tissue or organs due to enlargement of individual cells
– “trophe” = food overfed
– Hypertrophy in cardiac muscles of the heart (as in hypertension) and skeletal muscle (as in bodybuilders)
Hypertrophy
increase in size of tissue or organs due to an increased number of cells
Hyperplasia
Chronic stimulation – callus (corn) – overgrowth of stratum corneum
– Hormones – uterus (endometrial hyperplasia due to action of estrogen)
– Hyperplasic polyps of intestines; Benign prostatic hyperplasia in elderly men
Change of one cell type into another
– Eg. Smokers – columnar cells of the bronchial mucosa stratified squamous
epithelium
■ Reversible change
Metaplasia
– Disorderly arrangement of cells and nuclear change
– Can progress to neoplasia (Cancer)
Dysplasia
Causes:
– May occur as a result of an overload of endogenous metabolites or exogenous
material
– May have metabolic disturbances that prevent secretion of metabolic byproducts and normal secretions
– Very complex mechanisms
Intracellular Accumulations Three types of intracellular accumations 1. Anthracosis (coal/carbon particles) 2.Hemosiderosis 3. Lipid accumulation
early stages of black lung disease
– Exogenous material accumulation
– Seen in lungs of coal miners and cigarette smokers
Anthracosis
Accumulation of blood-derived brown pigment
Hemosiderosis
– Derived from hemolyzed red blood cells
– Eg. Hereditary hemochromatosis – genetic disorder of liver (overabsorption of iron
from food)
is the most well described age-associated change in the subcellular structure – it is an agingpigment granule found in high concentrations in old cells.
■ Lipofuscin
Two Reasons Why Cells Die
■ Irreversible cell injury – Necrosis: localized death of cells or tissues in a living organism ■ Coagulative ■ Liquefactive ■ Caseous ■ Enzymatic fat Necrosis ■ Apoptosis (“dropping out”) – Programmed cell death (single cells)
– Most common
– Cause: anoxia
■ Rapid inactivation of hydrolytic enzymes prevents lysis
– Outcome: cell membrane is preserved, organelles and nucleus coagulate
– Solid internal organs: heart, liver, kidneys
Coagulative Necrosis
Cause: cell is completely digested by hydrolytic enzymes – Eg. brain infarct
– Outcome: Dissolution of tissues soft and liquify
– Brain, skin, joints
Liquefactive Necrosis
Cause: Tuberculosis (TB) patients center part of tuberculous granuloma
becomes necrotic and cells fall apart
■ Cheesy
■ Also found with fungal infections (histoplasmosis)
– Lungs
Caseous Necrosis (special form of coagulative necrosis)
Caused by lipolytic enzymes and limited to fat tissues usually around the pancreas
– Cause: rupture of pancreas (acute pancreatitis)
■ Enzymes release into adjacent fat tissue degrade fat into glycerol and free fatty acids
■ Forms calcium soaps
■ Enzymatic Fat Necrosis
